Proteolytic enzymes are involved in a great variety of physiological processes. Proteases are generally classified according to their catalytic mechanisms. At least four mechanistic classes have been recognized, including the serine proteases, the cysteine proteases, the aspartic proteases, and the metalloproteases. The cysteine proteases can be grouped into at least 30 protein families including the plant proteases such as papain, actinidin or bromelain, several mammalian lysosomal cathepsins, the cytosolic calpains (which are calcium-activated) as well as several parasitic proteases (e.g those of Trypanosoma schistosoma). The X-ray structure of caspase-1 (also known as interleukin-1-beta converting enzyme) reveals a novel type of fold for cysteine proteases. Catalysis of the cysteine proteases proceeds through the formation of a covalent intermediate and involves a cysteine and a histidine residue (Cys25 and His159 under the papain numbering). The nucleophile is a thiolate ion, which is stabilized through the formation of an ion pair with the neighboring imidazolium group of His159. The attacking nucleophile is the thiolate-imidazolium ion pair in both steps.
The cysteine proteases are of great medical interest. Cysteine proteases in the papain family include mammalian enzymes such as cathepsins B and L, which are involved in cancer growth and metastasis, and cathepsin K, which is of importance for its involvement in bone degradation and osteoporosis. Other cysteine proteases are important enzymes for combating parasites because they are essential for the parasite-host interaction and are therefore attractive targets of inhibition such as cruzipain from Trypanosoma cruzi, which causes Chagas' disease, and falcipain from Plasmodium falciparum, which causes malaria. Other cysteine proteases such as those belonging to the legumain family, have been shown to play key roles in antigen presentation. Cysteine proteases of the caspase family are also of great interest as key mediators of apoptosis. Several cysteine proteases of pathogenic bacteria are virulence factors and cause severe problems for the host at infections, such as gingipains of Porhyromonas gingivalis, which is important in periodontitis, and streptopain from Streptococcus pyogenes. 
Therefore, the cysteine proteases have been considered important targets for the identification of therapeutics.